Chimeras are real and ethical

Oleg Lischuk, N+1 

In September 2014, the US National Institutes of Health (NIH) decided to cut off funding for experiments to create "chimeras" – animals with human tissues and organs. The leading organization for the regulation of medical research motivated this by the fact that it needs to assess in more detail the possible scientific and social consequences of such research. Officials are particularly concerned about the possibility of animals with human brain cells. However, scientists do not give up and are looking for alternative ways to create and study "chimeras".

Despite the "terrible" name, the purpose of creating "chimeras" is to save human lives. By planting human stem cells in animal embryos at the earliest stages of development, researchers expect to grow full-fledged human organs for transplantation with their help.

Simplified, this process looks like this. In an animal embryo, the genes responsible for the development of a certain organ, for example, the liver, are turned off (this complex genetic engineering technology is still being improved, but in some cases it is used). Such an embryo will not be able to develop into a viable animal, however, if you plant several stem cells of a healthy animal of the same or another species (this process is called embryo complementation), the missing organ will develop from them. If we are talking about a person, with the help of such technology, it is theoretically possible to grow a pig or sheep with a liver that is genetically identical to the patient from whom the cells were taken.

All this is possible only if the embryo is "processed" several days old (it is about a dozen cells), and then transferred to the uterus of the animal for gestation. The fact that "chimerization" occurs at such an early stage of development raises concerns: will human cells develop into something other than the desired organ, and will the animal turn out to be too "humanized". Studies that use two different types of animals show that this does not happen in practice – for example, mice with rat pancreas and other "chimeric" animals are grown. This can be confirmed for human organs only in a direct experiment.

Such experiments immediately come to the attention of all kinds of ethical committees, religious organizations, animal rights defenders, etc., which, of course, are opposed. Nevertheless, they are still held. According to MIT Technology Review (Human-Animal Chimeras Are Gestating on U.S. Research Farms), during 2015, about 20 pig and sheep embryos with human cells were created and transferred to the United States for gestation. Preliminary information about them was provided by the University of Minnesota and the Salk Institute in La Jolla, California. Several dozen more such experiments were presumably conducted outside the country. In all cases, pregnancy was terminated at an early stage, when the embryo already has rudimentary organs suitable for study, but it is not yet viable. There are no full-fledged scientific publications about these studies yet. (In fact, there are, albeit a little; see popular articles, for example, here or here – VM.)The most recent experiment to create "chimeras" was started at Stanford University by Japanese biologist Hiromitsu Nakauchi.

It was he who managed to breed mice with a rat pancreas in his homeland, but such experiments with human cells are prohibited in Japan, and the scientist moved to the United States. He told the MIT Technology Review correspondent that in 2015 he transplanted human induced pluripotent stem cells (iPS cells) to pig and sheep embryos. A grant for this study was allocated by the California Institute of Regenerative Medicine.

According to Nakauchi, the number of human cells in his experiment is relatively small. "If an embryo has 0.5 percent of human cells, it is extremely unlikely to get a thinking pig or an upright sheep out of it," he said, adding that he uses his own blood to obtain iPS cells. (iPS cells are obtained from the blood or skin of an adult organism. They can develop into many tissues, which brings them closer to embryonic stem cells. John Gurdon and Shinya Yamanaka received the Nobel Prize in 2012 for developing the technology for their production).

So far, there is no question of growing full–fledged "chimeras" - current experiments should show whether the development of a human organ in an animal's body is possible in principle, and how to create the most suitable conditions for this. In addition, they should provide the basis for sound ethical conclusions on this issue.

Nakauchi is confident that the work on obtaining "chimeras" does not pose a risk to society, but may in the future solve the problem of a shortage of organs for transplantation. Moreover, the organs grown in this way will be genetically identical to the patient's organs and will not be rejected by his immune system, and they can be grown within a year.

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11.01.2015